Decreased epithelial Progesterone Receptor A at the window of receptivity is required for preparation of the endometrium for embryo attachment. Mus musculus

The progesterone receptor A (PGRA) isoform is the dominantly expressed isoform within the mouse uterus and is indispensable for uterine function and fertility in the murine reproductive tract. During early pregnancy, the PGRA isoform is spatiotemporally expressed in the uterine epithelium. At days 2-3 of pregnancy, PGRA is upregulated within the epithelium and then decreases before day 4, the day of embryo implantation. This decrease of PGRA has been recognized as a marker to initiate the time in which the uterus is receptive to the embryo, yet this has never been functionally tested. We hypothesized the decrease of PGRA at the window of receptivity is required for successful embryo implantation. In order to test this hypothesis, we generated a PGRA conditional expression allele initiated by Cre recombinase present in the uterine epithelial compartment. The PGRA expressing mice exhibited infertility with the inability to undergo embryo implantation or decidualization. RNA microarray and ChIP-Seq analyses were utilized to identify the differentially regulated pathways controlled by PGRA at the time of implantation. Overall design: Mice exhibiting overexpression of PGRA in the uterine epithelium and littermate controls were mated to vasectomized male mice. Upon the presence of the post-coital plug, mice were sacrificed 4 days later and uterine horns were harvested and frozen. RNA was isolated from the uterus and pooled. An Agilent RNA microarray was performed on samples individually consisting of 3 pooled samples. Therefore, 9 mice are represented in total per genotype.